1445P A randomized phase III trial on Pembrolizumab Alone versUs pembrolizumab-chemotherapy in first LInE NSCLC (PAULIEN), results of the interim analysis

To date, first-line pembrolizumab monotherapy (PEM) has not been compared to pembrolizumab + chemotherapy (PEM/CT) in metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥50%. However, the regimen that provides the highest response rate, crucial for when a tumor response is urgently needed, is unknown. Here, we report the interim results of the PAULIEN study (NTR 8896), aiming to identify the regimen (PEM or PEM/CT) with the highest response rate. This open label, phase 3, multicenter trial aimed to randomize (1:1) 84 patients with untreated metastatic NSCLC with PD-L1 TPS ≥50% and a high tumor burden to receive PEM (200mg fixed, 3 or 6 weekly) or PEM (200mg fixed, 3 weekly) + platinum-based chemo-doublets with either pemetrexed or paclitaxel. Pemetrexed and PEM were continued as maintenance therapy. Patients in the PEM arm received CT after progressive disease. Stratification factors included age, performance status, T-stage and histology. Co-primary endpoints were objective response rate (ORR) and disease control rate (DCR) at week 6 and 12 per RECIST v1.1. Secondary endpoints included progression-free survival, overall survival and safety. A planned interim analysis was performed (data cut-off March 1st, 2023). 50 patients were randomized to PEM (n=19) and PEM/CT (n=31). Baseline characteristics were well balanced between arms. 42 patients were radiologically evaluable of whom 17 patients received PEM and 25 patients PEM/CT. The PEM arm demonstrated an ORR at week 6 of 38% vs. 44% in the PEM/CT arm (p=0.68) and a DCR of 88% vs. 88% (p=1.0). At week 12, the PEM arm demonstrated an ORR of 74% vs. 68% in the PEM/CT arm (p=1.0) and a DCR of 93% vs. 91% (p=1.0), respectively. The incidence of grade 3-4 treatment-related adverse events was 28% (PEM) vs. 52% (PEM/CT). No treatment-related deaths occurred. In this interim analysis, the tumor response rate with first-line PEM alone was comparable to that of PEM/CT in metastatic NSCLC patients with PD-L1 TPS ≥50%,. No new safety signals were observed. More data is needed to explore subgroups that may still benefit from adding chemo to PEM in this population.